An antibiotic substance is indispensable to control a microorganism and to cure an infective disease. However, excessive use of an antibiotic substance produces a resistant bacterium thereto, resulting in producing a multiple-drug-resistant bacterium having resistances to many drugs; and thus, it becomes a serious clinical problem. Especially methicillin-resistant Staphylococcus aureus (hereinafter abbreviated as MRSA) appears often in a clinical site, and thus, it became a social problem. Furthermore, Enterococcus having a resistance to vancomycin which is often used as a final therapeutic drug to MRSA (hereinafter the said vancomycin-resistant Enterococcus is abbreviated as VRE) has been separated from a clinical site in this country; and thus, a new therapeutic drug for a multiple-drug-resistant bacterium is eagerly wanted.
Especially, emergence of VRE which shows a resistance to vancomycin, the effective drug for MRSA, is considered to be a serious problem. This is assumed because Enterococcus itself resides always in the intestinal tract so that a potential carrier of the bacterium may be generated readily whereby a resistance gene thereof is transmitted to other bacterium due to long time residence in a patient body, and this in turn leading to increase of a risk to generate vancomycin-resistant Staphylococcus aureus (VRSA) and so on.
Separately from the problem of emergence of a resistant bacterium, an antibiotic substance having substantially high therapeutic effect while having higher safety than vancomycin and so on is eagerly wanted; and thus, an investigation is progressing to obtain a novel antibiotic substance not only being effective to MRSA and VRE but also having higher safety with less side effects and so on as compared with existing drugs.
As to the new therapeutic drug like this, linezolid, a synthetic antibiotic substance obtained by a total chemical synthesis method has been known. In addition, many investigations to find out an antibiotic substance showing effectiveness to the foregoing multiple-drug-resistant bacteria from antibiotic substances which are produced by various microorganisms have been carried out (Patent Documents 1 to 3). Among these Documents, in Patent Documents 1 and 2, a microorganism belonging to a genus Lysobacter which produces an antibiotic substance showing effectiveness to the foregoing multiple-drug-resistant bacterium and a method for producing the antibiotic substance by using this microorganism are described.
To achieve the foregoing object, not only creation of an antibiotic substance having a novel chemical structure and synthetic exploration of betterment and so on of existing antibiotic substances but also exploration of a novel microorganism capable of producing a useful and novel antibiotic substance which has not been reported before is being carried out widely. This is because an antibiotic substance produced by a microorganism is a natural substance produced in a living body, so that the substance is assumed much safer to a living body as compared with a chemically synthesized substance.
As to the microorganism which produces a novel antibiotic substance, many kinds of microorganisms have already been reported; and the microorganism belonging to a genus Lysobacter of Xanthomonadaceae, which is used in the present invention, has been reported as such a microorganism in Patent Documents 1, 2, 5, and so on. Among those Documents, in Patent Documents 2 and 5, a microorganism which produces an antibiotic substance having an antibacterial activity to the foregoing multiple-drug-resistant bacteria and a method for producing the antibiotic substance by using the said microorganism are described.
To provide a novel antibiotic substance not only having an antibacterial activity to methicillin-resistant Staphylococcus aureus (hereinafter abbreviated as MRSA) and vancomycin-resistant Enterococcus (hereinafter abbreviated as VRE), which are especially problematic in clinical site among the multiple-drug-resistant bacteria, but also showing an excellent therapeutic effect is eagerly wanted. However, most of the antibiotic substances which so far have been reported effective to the multiple-drug-resistant bacteria are those showing an antibacterial activity only to MRSA; there are not so many reports about the antibiotic substance also showing an antibacterial activity to VRE at the same time. As to example of the antibiotic substance effective both MRSA and VRE, an antibiotic substance showing an in vitro antibacterial activity to both the foregoing multiple-drug-resistant bacteria (hereinafter, antibacterial activity means “antibacterial activity shown in vitro” unless otherwise noted) is described among the antibiotic substances reported in Patent Document 3.
In addition, a novel microorganism belonging to a genus Lysobacter and a novel antibiotic substance produced and manufactured therefrom are described in Patent Documents 1 and 2; a novel microorganism belonging to a genus Flavobacterium and a novel antibiotic substance produced and manufactured therefrom are described in Patent Document 6; and a novel microorganism belonging to a genus Streptomyces and a novel antibiotic substance produced and manufactured therefrom are described in Patent Document 7.
On the other hand, inventors of the present invention constructed the “silkworm Staphylococcus aureus infection model” (Patent Document 4) by using, as an experimental animal, a silkworm (a larva of Bombyx mori), wherein the model was effectively used to explore an antibiotic substance; and then he carried out investigation on it.    Patent Document 1: Japanese Patent No. 3339235    Patent Document 2: Japanese Patent No. 4054576    Patent Document 3: Japanese Patent No. 4057426    Patent Document 4: Japanese Patent Laid-Open Publication No. 2007-327964    Patent Document 5: Japanese Examined Patent Application Publication No. H06-99444    Patent Document 6: Japanese Patent Laid-Open Publication No. 2003-113192    Patent Document 7: Japanese Patent Laid-Open Publication No. 2007-131552